Double Dose 4-AP on Functional Recovery After Spinal Cord Injury

Shirley Ryan AbilityLab

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: SCI - Spinal Cord Injury

Treatments: Behavioral: Exercise training; Drug: Placebo; Other: STDP stimulation; Drug: Dalfampridine

Study type: Interventional

Funder types: Other

Identifiers

NCT06853015

STU00221545

Details and patient eligibility

About

The purpose of this study is to test a strategy to potentiate functional recovery of lower limb motor function in individuals with spinal cord injury (SCI). The FDA approved drug, Dalfampridine (4-AP). 4-AP will be used twice-daily in combination of Spike-timing-dependent plasticity (STDP) stimulation and STDP stimulation with limb training.

Full description

Currently, research has shown that 4-AP has a positive effect on sensory and motor function rehabilitation in humans with chronic SCI in addition to decreasing recorded spasticity, increased sensation, and decreased pain. A pharmacokinetic study showed that twice-daily administration of sustained release 4-AP maintains a steadier plasma concentration. Utilizing limb training to promote recovery of motor function is enhanced by eliciting STDP in the limbs. An important strength of this aim is the combination of training and STDP, which aims to enhance the beneficial effects of motor training by promoting plasticity in the corticospinal pathway. Training effects on physiological pathways will be explored and correlated with lower limb motor function. We hypothesize that introducing 4-AP into the STDP stimulation and STDP stimulation with training will further improve motor function rehabilitation in patients with chronic SCI.

Enrollment: 27 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male and females between ages 18-85 years
• SCI 6 months post injury
• Spinal Cord injury at or above L2
• ASIA A, B, C, or D, complete or incomplete
• The ability to perform a small visible contraction with dorsiflexion and hip flexor muscles

Exclusion criteria

• Uncontrolled medical problems including pulmonary, cardiovascular or orthopedic disease
• Any history of renal impairment
• Any debilitating disease prior to the SCI that caused exercise intolerance
• Premorbid, ongoing major depression or psychosis, altered cognitive status
• History of head injury or stroke
• Vascular, traumatic, tumoral, infectious, or metabolic lesion of the brain, even without history of seizure, and without anticonvulsant medication
• History of seizures or epilepsy
• Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold (see appendix 2)
• Pregnant females
• If a women of child bearing age is unsure of the pregnancy, and does not want to take the pregnancy test
• Ongoing cord compression or a syrinx in the spinal cord or who suffer from a spinal cord disease such as spinal stenosis, spina bifida, MS, or herniated disk
• Metal plate in skull
• Individuals with scalp shrapnel, cochlear implants, or aneurysm clips
• Individuals taking Bupropion, Dolutegravir, Lacosamide, Trilaciclib, or PR Interval prolonging drugs

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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27 participants in 2 patient groups, including a placebo group

4-AP(AM) + STDP stimulation + training + 4-AP(PM)

Experimental group

Description:

The effects of the functional recovery of the lower-limb muscles will be determined after 40 sessions of twice-daily-dosing 4-AP, STDP stimulation and training.

Treatment:

Drug: Dalfampridine

Other: STDP stimulation

Behavioral: Exercise training

Placebo(AM) + STDP stimulation + training + Placebo(PM)

Placebo Comparator group

Description:

The effects of the functional recovery of the lower-limb muscles will be determined after 40 sessions of twice-daily-dosing Placebo, STDP stimulation and training.

Treatment:

Other: STDP stimulation

Drug: Placebo

Behavioral: Exercise training